BIOCH Y1 S1: Chromosome Disorders Flashcards
what is a karyotype
- an image of an individual’s collection of chromosomes
positions of centromere
- metacentric: in the centre (chromosomes 1-5)
- submetacentric: slightly above the centre (chromosomes 6-12)
- acrocentric: a lot above the centre (chromosomes 13-22)
- telocentric (satellites): essentially no P arm (not really found in humans)
what is an ideogram
- standardised numbering system for bands in G banding
- used for accurately describing locations of genes or abnormalities on a chromosome
- genes are numbered out from the centromere to the telomere
p arm vs q arm (chromosome)
- p: short arm (p for petite)
- q: long arm
what is G-banding
- alternating unique light and dark bands
- light bands contain most of the transcriptionally active genes (G/C rich) > wound looser > dye doesn’t pick it up
- dark bands are A/T rich
- can detect deletions or insertions > 4Mb
notation for karyotype
- total no. of chromosomes, sex chromosomes, description
- e.g. 46, XX, normal female
pter and qter
- pter: tip (terminal end) of short arm
- qter: tip of long arm
cen and del (ISCN nomenclature)
- centromere
- deletion
der and ins (ISCN nomenclature)
- derivative of chromosome rearrangement
- insertion
inv, mat and pat (ISCN nomenclature)
- inversion
- maternal origin
- paternal origin
what is aneuploidy + 3 types
- loss or gain of one or more chromosomes
- monosomy: loss of 1 chromosome, usually lethal b4 term
- trisomy: gain of 1 chromosome
- tetrasomy: gain of 2 chromosomes
how does aneuploidy arise?
- usually by non-disjunction (failure of chromosomes or sister chromatids to separate during anaphase (meiosis or mitosis)
mosaicism
- when there is a cell line with more than one karyotype due to aneuploidy arising during mitosis
- e.g. mosaic Down syndrome: some cells have trisomy 21, some cells are normal
examples of aneuploidies
SURVIVE GESTATION - AUTOSOMAL
(increased risk w/ mother’s age)
- Patau - 47 chromosomes, trisomy 13 (least common)
- Edward - 47 chromosomes, trisomy 18
- Down - 47 chromosomes, trisomy 21 (most common)
DON’T SURVIVE GESTATION - SEX
- Turner (female)- 45 chromosomes, X > short stature
- Kleinefelter (male) - 47 chromosomes, XXY > more feminine characteristics e.g. gynaecomastia, tall stature
polyploidy and 2 types
- n exceeds normal ploidy level, not compatible w/ life
- triploidy: 3n = 69
- tetraploidy: 4n = 92
causes of polyploidy
- fertilisation of egg by 2 sperms
- fertilisation of egg by diploid sperm
- fertilisation of diploid egg by sperm
2 categories of chromosome abnormality
- number abnormality (polyploidy, aneuploidy)
- structural abnormality - chromosome breakage w/ rejoining in a diff location
5 types of structural abnormalities
- insertion
- deletion
- inversion
- translocation (swapping b/n chromosomes)
- duplication
balanced rearrangement
- no net gain or loss of chromosomal material e.g. inversion or reciprocal translocation
- usually harmless for the patient unless an important gene is interrupted
- carriers are at risk of producing offspring w/ UNbalanced rearrangement/miscarriage
unbalanced rearrangement
- net gain or loss of chromosomal material e.g. insertion, deletion, translocation, duplication
- usually severe clinical effects
cri-du-chat (CdC) syndrome
- deletion of 5p15 (chromosome 5, p arm, band 15)
- cat-like cry and facial dysmorphisms
3 types of translocation
- reciprocal: exchange of parts b/n non-homologous chromosomes (balanced)
- Robertsonian: long arms of 2 acrocentric chromosomes fuse, short arms are lost > 1 large metacentric chromosome (balanced) - centromere breaks
- insertional/non-reciprocal: deletion of a chromosome inserted to another (unbalanced)
how to tell autosomal recessive vs autosomal dominant on a pedigree
- recessive: an affected individual w/ 2 unaffected parents (skipped generation)
- dominant: every affected individual has an affected parent
- both have equal males and females affected
how to tell x linked dominant vs x linked recessive
- dominant: affected father passes onto all daughters, more females may be affected
- recessive: affected mother (heterozygous) passes onto 50% of her sons, more males affected
how to tell if its y-linked
- no affected women
- all males are affected
how to tell if its a mitochondrial inheritance
- affected female transmits to some children
- affected males do not pass on
what is X-inactivation
- since females have 2 copies of the X chromosome but males only have one, 1 of the female copies is inactivated
- therefore males and females express approx the same amount of X genes
types of mutations (protein outcome)
- silent: diff codon but same AA b/c code is redundant (often seen in the 3rd/wobble base in the codon)
- missense: one different AA (usually 1st or 2nd base of codon)
- nonsense: early stop codon
- frameshift: totally new protein
- inframe deletion: delete 3 bases
proband
- first person in family to be diagnosed w condition in a pedigree
loss of function vs gain of function mutations
- loss: negatively affect protein function (generally recessive)
- gain: altered function (not necessarily +ve, generally dominant)
conditional mutations
cause phenotypic changes under certain conditions but not detectable under permissible conditions
monogenic vs polygenic (multifactorial) conditions
- monogenic: single defective gene
- multifactorial: genetics combined with environmental factors (epigenetics)
how does autism work?
- variation in several genes
